Variant 11-49054157-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206631.1(TRIM64C):c.910G>A(p.Glu304Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TRIM64C
NM_001206631.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

TRIM64C (HGNC:37148): (tripartite motif containing 64C) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM64C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1589047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM64C	NM_001206631.1 linkuse as main transcript	c.910G>A	p.Glu304Lys	missense_variant	6/6	ENST00000617704.1	NP_001193560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM64C	ENST00000617704.1 linkuse as main transcript	c.910G>A	p.Glu304Lys	missense_variant	6/6	5	NM_001206631.1	ENSP00000481815	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

156392

Hom.:

AF XY:

0.0000121

AC XY:

AN XY:

82758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399262

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.910G>A (p.E304K) alteration is located in exon 6 (coding exon 6) of the TRIM64C gene. This alteration results from a G to A substitution at nucleotide position 910, causing the glutamic acid (E) at amino acid position 304 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.71

M_CAP

Benign

0.0063

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

Sift4G

Benign

0.15

Vest4

0.19

MVP

0.17

ClinPred

0.11

GERP RS

1.3

Varity_R

0.039

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over